Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Clinical Profile and Severity of Hemolysis in Adult Patients of Primary Autoimmune Hemolytic Anemia and Their Response to Steroid: A Prospective Cohort Study from Single Institution

Autoimmune hemolytic anaemia (AIHA) has traditionally been classified based on the temperature sensitivity of the autoagglutinins as warm (WAIHA), cold (CAIHA) and mixed type. Autoagglutinin may be of IgG or IgM type. The present prospective study was conducted to evaluate the profile of clinical picture, severity of haemolysis, treatment response of steroid. This study on patients of adult primary AIHA was conducted by taking complete history followed by detail physical examination. Laboratory investigations were performed to establish haemolytic anaemia and to assess severity of haemolysis. Immunehematological work up including blood grouping, direct antiglobulin test (DAT), IAT, antibody screening, adsorption elution was performed to diagnose type of AIHA. All cases were followed up to assess the response to prednisolone. All the data were collected and analysed by SPSS 19. Out of 62 primary AIHA cases, female were affected more than male (41:21). WAIHA is most common type (42, 67.8%) followed by mixed (20.9%) and cold AIHA (11.3%). Severity of haemolysis showed significant correlation with the DAT strength and not with type of AIHA. (P < 0.05) On oral prednisolone, 22 cases attended complete remission, while relapse, drug dependency and partial remission was achieved in 13, 9, 3 cases respectively. Severity of haemolysis in AIHA is directly related with DAT strength. WAIHA is most common type and can be managed with oral prednisolone (cr 45.2%), without red cell transfusion in most of cases. Mixed type AIHA cases were presented mostly with severe haemolysis, with minimum therapeutic response to prednisolone and maximum relapse/drug dependency.     

Study on influence of age,gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians

Background: Lactase non-persistence (LNP) has been associated with the CC genotype of ?13910C?>?T and GG genotype of ?22018G?>?A polymorphisms present upstream of the lactase gene. Lactose intolerance (LI) is caused when gastrointestinal symptoms develop in individuals with low lactase activity.

Objective: To analyse association of LNP genotype and LI symptoms with milk intake and determine whether factors such as age, gender and genotype affect LI status.

Subjects and methods: Genetic analysis and lactose tolerance test (LTT) were performed on 205 healthy Indian adults. The pattern of milk consumption was recorded using a dietary questionnaire.

Results: LI was strongly associated with ?13910CC genotype (OR?=?10.28, 95% CI?=?2.32–45.55, p?=?0.002). Females were found to be at a higher risk of developing LI (OR?=?2.47, 95% CI?=?1.33–4.59, p?=?0.004). The association of the ≥50 years age group with LI was marginally significant (OR?=?1.86, 95% CI?=?0.995–3.47, p?=?0.05). Frequency and quantity of milk intake were lower in subjects belonging to the LNP genotype and LI groups (p?Conclusions: Subject study suggests that gender and genotype may be associated with development of LI. Association of age with LI was marginal. The data also indicate that LNP genotype and LI may play a role in influencing milk intake in individuals.     

Cervical squamous intra-epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India

In view of the dual burden of HIV infection and cervical cancers in India, this study was undertaken to estimate the prevalence of Pap smear abnormalities and human papillomavirus infection among HIV-infected women. Consecutive HIV-infected women attending voluntary counseling testing clinics were enrolled. Written informed consent, demographic information, Pap smears, cervical swabs for HPV typing and a blood sample for CD4+ cell count were collected. Treatment for opportunistic and sexually transmitted infections and reproductive tract infections was provided. Women with Pap smear abnormality were referred for further intervention. Between January 2003 and May 2004, 287 HIV-infected women were enrolled. Pap smear abnormalities were seen in 6.3% women and were more common among women aged 30 and above (P=0.042) and those who had suffered from opportunistic infections (P=0.004). In multivariate analysis, Pap smear abnormalities were associated independently with opportunistic infections (P=0.02, AOR 3.8, 95% CI 1.2--11.5). Of the 100 random cervical specimens screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9--43.1) were positive for HPV 16/18. Of the 122 patients who returned for a follow-up visit, 5 patients (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100 person year of follow-up. In order to prevent thousands of deaths due to cervical cancer in India, there is a need for strengthening the Pap smear screening program and HPV vaccine development.     

An Experimental Model for the Study of Lymphedema and its Response to Therapeutic Lymphangiogenesis

BACKGROUND: Evaluation of the efficacy of molecular treatment strategies for lymphatic vascular insufficiency requires a suitable preclinical animal model. Ideally, the model should closely replicate the untreated human disease in its pathogenesis and pathological expression. OBJECTIVE: We have undertaken a study of the time course of the development and resolution of acquired, experimental lymphedema and of its responses to vascular endothelial growth factor (VEGF)-C lymphangiogenesis in the mouse tail model. STUDY DESIGN: We provoked post-surgical lymphedema in the mouse tail model and assessed the effects of exogenously administered human recombinant VEGF-C. Quantitative assessment of immune traffic function was performed through sequential in vivo bioluminescent imaging. RESULTS: In untreated lymphedema, tail edema was sustained until day 21. Exogenous administration of human recombinant VEGF-C produced a significant decrease in volume. Untreated lymphedema in the mouse tail model was characterized by the presence of dilated cutaneous lymphatics, marked acute inflammatory changes, and hypercellularity; VEGF-C produced a substantial reversion to the normal pattern, with notable regression in the size and number of cutaneous lymphatic vessels that express lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). In vivo imaging confirmed the presence of an impairment of immune traffic in lymphedema that was ameliorated after VEGF-C administration. CONCLUSION: The post-surgical murine tail model of lymphedema closely simulates attributes of human lymphedema and provides the requisite sensitivity to detect therapeutically induced functional and structural alterations. It can, therefore, be used as an investigative platform to assess mechanisms of disease and its responses to candidate therapies, such as therapeutic lymphangiogenesis.     

Human Immunodeficiency Virus and Leprosy Coinfection in Pune,India

We report eight cases and the incidence of leprosy in human immunodeficiency virus (HIV)-infected individuals after initiation of antiretroviral treatment (ART). The incidence of leprosy in patients on ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28). This high incidence suggests that there should be regular examination of HIV-infected individuals for clinical signs of leprosy.Although there is a declining trend in the global burden of leprosy, there are 15 countries in Asia and Africa which account for 94% of the global total of the new-case detection rate. India is one of the countries where ≥1,000 new cases of leprosy were reported during 2006 (14). Human immunodeficiency virus (HIV) and leprosy both are feared due to the associated social stigma, and leprosy can manifest as immune reconstitution inflammatory syndrome (IRIS) in HIV-infected individuals (9). The first case of leprosy-associated immune reconstitution disease was reported in 2003 for a Ugandan living in London, United Kingdom (5). Later leprosy was described as a manifestation of IRIS in many instances (8, 10).Antiretroviral treatment (ART) for HIV infection is now available in resource-poor regions where leprosy is still endemic, such as South America, Africa, and Asia, including India. India accounts for half of the world''s leprosy cases due to its population of more than 1 billion, even though a nationwide prevalence of less than 1 case/10,000 population was reported in 2005 (4). In addition, India also has the third largest burden of HIV-infected individuals (12). In spite of having a large burden of both leprosy and HIV, there are very few published reports of HIV-leprosy coinfection from India. We report eight cases of incident leprosy in HIV-infected patients who were on ART and the incidence of leprosy in HIV-infected individuals on ART.This report is from the Amrita Clinic of PRAYAS, a nongovernmental organization working on HIV/AIDS in Pune, in the state of Maharashtra, India. We retrospectively analyzed data on HIV-infected patients who initiated ART between January 2003 and December 2006 and we studied their follow-up till December 2007 to evaluate the incident cases of leprosy. ART was provided following the national guidelines for treatment of HIV infection (7).Diagnosis of leprosy was based on the clinical signs and symptoms and demonstration of acid-fast bacilli in the slit skin smears by Ziehl-Neelsen staining. All patients with leprosy received multidrug treatment per the WHO guidelines (15).Several definitions of IRIS have been utilized, each incorporating the general concept that cases of IRIS need to have an inflammatory component occurring in the setting of immune reconstitution that cannot be explained by drug toxicity or a new opportunistic infection (1, 6). We have considered leprosy manifestation after starting ART with increase in CD4⁺ cell count, inflammatory response as seen by neuritis, type I or type II leprosy reaction, or need for the use of steroids for the control of inflammation as a criterion for defining leprosy manifestation as IRIS. Statistical analysis was done using STATA (version 8.0).Between January 2003 and December 2006, among the 1,002 HIV-infected patients who started ART for HIV infection and were followed up till December 2007, eight incident cases of leprosy were detected. None of them had clinical evidence of leprosy at the time of initiation of ART. Table ​Table11 describes the details of these eight patients. All the patients except for one were males, and the mean age of the patients with leprosy was 33.8 years (standard deviation [SD], 5.1 years; range, 27 to 42 years). Four patients had paucibacillary leprosy, and four patients had multibacillary leprosy. The mean CD4⁺ cell count of incident leprosy cases was 326 (median, 245; SD, 255.5; range, 99 to 892). Of these eight patients, three had other opportunistic infections such as pulmonary tuberculosis, abdominal tuberculosis, and herpes zoster. The mean number of months to develop leprosy after starting ART was 13.8 months (SD, 14.3 months; range, 2 to 43 months). All eight patients completed their leprosy treatment and recovered completely. Although eight patients developed incident leprosy, six of them developed leprosy within 2 years of starting ART and two patients had delayed manifestations, with one patient developing leprosy after 28 months and the other after 43 months. These 1,002 patients on ART contributed to 1,532.5 person-years, and hence, the overall incidence of leprosy after starting ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28).

TABLE 1.

Details of HIV-infected patients on ART with incident leprosy^a

Two‐Colored Dental Surveying Tool as an Alternative for Carbon Marker

Various tools are used with a dental surveyor, including analyzing rods, carbon markers, undercut gauges, and protective sheaths for a specific function. A carbon marker is a parallel‐sided carbon rod used to mark the survey line on a cast or a crown on a cast. The carbon marker (with or without protective sheath) cannot differentiate more than one survey line on the cast if needed. The wear of the carbon marker along the parallel walls after repeated use may give an incorrect survey line. We suggest a simple modification in the analyzing rod to prepare a two‐colored surveying tool. An analyzing rod is a parallel‐sided rod used to analyze the relative parallelism of two or more surfaces of a cast and to mark survey lines on wax patterns. With the modified analyzing rod, the survey lines can be marked with two colors, and the problem of breaking of the carbon marker also can be eliminated.     

Diabetic mastopathy

Diabetic mastopathy is the occurrence of lymphocytic mastitis and stromal fibrosis in men as well as women having long-standing diabetes. Clinical and radiological appearance can raise a suspicion of malignancy and result in unnecessary biopsy. As these lesions are known to recur; failure to recognise them can have devastating results. A case of diabetic mastopathy is therefore presented for the knowledge and benefit of all so that unnecessary surgery can be avoided.